Publication Date:
1998-06-11
Description:
Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta-ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mdluli, K -- Slayden, R A -- Zhu, Y -- Ramaswamy, S -- Pan, X -- Mead, D -- Crane, D D -- Musser, J M -- Barry, C E 3rd -- AI37004/AI/NIAID NIH HHS/ -- Z01 AI000783-11/Intramural NIH HHS/ -- New York, N.Y. -- Science. 1998 Jun 5;280(5369):1607-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tuberculosis Research Unit, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases (NIAID), National Institutes of Health, Hamilton, MT 59840, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9616124" target="_blank"〉PubMed〈/a〉
Keywords:
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/*antagonists &
;
inhibitors/chemistry/genetics
;
Acyl Carrier Protein/chemistry/genetics/metabolism
;
Amino Acid Sequence
;
Antitubercular Agents/*pharmacology
;
Drug Resistance, Microbial
;
Enzyme Inhibitors/pharmacology
;
Fatty Acids/metabolism
;
Genes, Bacterial
;
Humans
;
Isoniazid/*pharmacology
;
Molecular Sequence Data
;
Molecular Weight
;
Mutation
;
Mycobacterium tuberculosis/drug effects/*enzymology/genetics
;
Mycolic Acids/metabolism
;
Tuberculosis/microbiology
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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